When you face an enemy that is both elusive and ubiquitous, information is the best defense. You need early warning. And you need to know not only when trouble’s coming, but what it is and where it came from. Such is the case on the front lines of the battle against emerging diseases and bioterror attacks, where cutting-edge technology and wide-ranging surveillance programs are helping us actively defend against the threats.
There are outlaw regimes or terror networks hunting for or already building biological weapons programs. What if we could identify the deadly products they made by their biological “fingerprints,” so that we could analyze — fast — where anthrax mailed to a senator came from and how deadly it was? Attacks might even be prevented if our enemies knew, for example, that we know which anthrax is their anthrax.
If bird flu or some other deadly new viral pandemic reached our shores, what if we had the ability to test samples to precisely identify, track and develop defenses against that particular bug? Or what if we had a way to actually forecast what new viruses will emerge so we could prevent an outbreak from even occurring?
In both cases, thousands of lives could be saved. And Bruins could very well be the heroes that save those lives.
UCLA already is a major player in the effort to develop readiness plans in the event of a biological crisis [“Flu Fighters,” UCLA Magazine, October 2006]. Now it also is fast becoming one of the most critical information and tracking centers in the nation’s defense against these deadly threats.
The School of Public Health’s (SPH) High Speed, High Volume Laboratory Network for Infectious Diseases is the first of its kind — a rapid response science resource that can track thousands of bioterror threats or infectious disease outbreaks almost in real time, identify their origins and shorten the time needed to produce vaccines.
And the National Institutes of Health has tasked the SPH to create the Center for Rapid Influenza Surveillance and Research (CRISAR), which will direct a team of physicians, veterinarians, researchers and biologists assembled from across the United States to investigate and identify flu viruses with the potential to explode into pandemics.
In this critical battle, Westwood’s clinicians, biologists, infectious disease specialists, epidemiologists and other disease fighters represent a new kind of scientist-scholar for the 21st century. These are not just researchers. They are real-life science action heroes.
“There’s no question but that the globalization of society has created new, more imminent public health challenges,” says Linda Rosenstock, the dean of UCLA’s School of Public Health. “The school is undertaking truly visionary work not just with respect to responding to these threats, but seeking ways to prevent them.”
The Bug Hunters
One of the hottest young foot soldiers in the war on disease is Nathan Wolfe, a professor of epidemiology in the School of Public Health and a new arrival from Johns Hopkins University. This is no ivory-towered academic. This is the very model of the scientist as action hero.
The adventurous epidemiologist worked with hunters in Cameroon, out in the jungle gathering scientific evidence, talking with tribal elders and trading like a native — one of his academic mentors called Wolfe a “ferocious bargainer” in an April 2007 profile in The Scientist. And the curly-haired scientist’s Web site homepage opens with a huge headline declaring, “The HIV pandemic could have been averted. Our work may prevent the next one.”
In May 2007, Wolfe, who received his doctorate in 1998 from Harvard University, teamed with UCLA Professor of Medicine and Infectious Diseases Claire Panosian Dunavan and iconic UCLA Geography Professor Jared Diamond — the Pulitzer Prize-winning author of Guns, Germs, and Steel, among other notable books — to report the first systematic analysis of the origins for all major human diseases. Their report, which also described the five-step process by which viruses jump from animals to humans and then become established, showed that the majority of infectious diseases for which origins could be identified had animal origins.
“The only real choices are either it comes from animals or it comes from your ancestors,” says Wolfe. “You would really expect some of these diseases to be ancient diseases. Some of them are quite old, but all of them at some point crossed over from an animal to humans or our ancestors.”
The finding is helpful in telling us about how to actually forecast disease-related threats before they appear, an early-warning approach that so far usually is reserved for physical or climatic phenomena (think of tornado warnings or all the global warming predictions). Wolfe wants to establish the first global surveillance network for the transmission of new viruses. Two years ago, he was awarded a Director’s Pioneer Award from the National Institutes of Health to do just that.
Researchers have dubbed this “viral forecasting,” in which the patterns associated with the previous emergence of viral diseases — say, HIV or influenza — are used to predict the emergence of future diseases. And, most importantly, to prevent them.
“Let’s say that there are going to be 50 new diseases over the next 50 years,” Wolfe explains. “If you hit [just] one or two of those, it will justify [the effort] because of the benefits you get from prevention ... and it’s not just individual medicine. It’s also population-level medicine.”
Wolfe’s surveillance network, for example, is coordinating with researchers in a number of other countries that are known to be hot spots for emerging disease. His first site is in Cameroon, where he and his collaborators are studying retroviruses such as HIV, pox viruses such as smallpox, and filoviruses like Ebola, along with plasmodium (the single-celled parasites that cause malaria), bacteria and a number of other disease-causing organisms. The network also includes China, home to countless wild animal markets where the close proximity of animal hosts and humans increases the chance of diseases jumping species, and Malaysian Borneo, where Wolfe did his doctoral research.
Once samples of disease-causing organisms are obtained in the field in these countries and at sites in places like Madagascar, Laos and New Guinea, the data is collected in a kind of viral museum in Wolfe’s lab and analyzed to reveal underlying patterns about the nature of the organisms.
Wolfe isn’t the only Bruin out in the field, or the jungle, helping to keep the home front safe. In the Democratic Republic of Congo, the disease surveillance program led by epidemiologist Anne Rimoin M.P.H. ’96, an assistant professor in the School of Public Health, is investigating cases of monkeypox and other zoonotic agents (agents that can be transmitted from animals to humans).
Rimoin’s undergraduate degree was in African history, which she admits had a lot to do with her scientific journey to search for and defend against emerging diseases in Africa. The scientist also worked in Africa while in the Peace Corps and for the World Health Organization. Among her accomplishments — training Peace Corps volunteers to do disease surveillance in the field. She describes the Democratic Republic of Congo as the “cradle of emerging disease.”
“Monkeypox is the perfect example of a viral zoonotic emerging infection,” Rimoin explains. “It is clinically indistinguishable from smallpox, so no one really knows when it first appeared.” Once smallpox was officially eradicated in 1979, however, and blanket immunization for the disease ceased, the previously rare monkeypox — which also can be prevented with the smallpox vaccination — began causing larger, more severe outbreaks.
The disease is becoming increasingly prevalent for a number of reasons: the absence of smallpox vaccinations among individuals under age 30; high rates of HIV infection and its accompanying immune system suppression; an increasing dependence on bush meat (monkey meat); and urbanization. “That’s why a disease like monkeypox is not only interesting, but important in many ways. It’s a harbinger of what happens when you have a whole population that is susceptible to a disease-causing organism,” Rimoin says.
Back in Westwood, a similar diligence on the part of clinicians and others on the medical front line could detect new disease threats, argues David Pegues, a professor of clinical medicine and the director of the UCLA Hospital Epidemiology Program. For example, Pegues advocates the coordinated collection of emergency room discharge data — which contains vital diagnostic information, such as viral culture results — and other readily available electronic data.
A “Surge” Protector
“If you could filter that data, you’d come up with a better idea of what is going on,” he says. In addition, Pegues would like to see hospitals actively encouraging clinicians to routinely take cultures from all individuals with symptoms of influenza-like illness. It’s not enough, he says, to diagnose a case of influenza based only on the presence of fever, headache, chills, muscle ache and other flu symptoms; viral diagnostic tests should be used to determine exactly with what organisms and strains patients are infected.
UCLA professor of epidemiology Scott Layne and his colleagues are now setting up a unique, first-of-its-kind laboratory to perform that analysis. UCLA’s High Speed, High Volume Laboratory Network for Infectious Diseases, created in collaboration with Los Alamos National Laboratory, is being designed to track bioterrorism attacks and infectious disease outbreaks in near real time, and dramatically decrease the time needed for vaccine production. When it is completed next year, the fully automated laboratory, also known as the rapid throughput lab, will analyze bar-coded samples collected nearly anywhere in the world, and have the capacity to determine the full genetic sequence of some 50 viruses per day. One benefit of the new lab is that it will have the ability to quickly analyze huge numbers of samples of anthrax and other agents of bioterror, a capacity known as “surge” ability.
The lab’s speed is vital for studying influenza because of the high genetic variability among flu subtypes and their propensity to quickly mutate (which is why new vaccines must be developed yearly). “We currently don’t know what makes a particular flu virus virulent and a threat,” says Layne, who is also the principal investigator of CRISAR. “The premise of the new lab is that with enough information, we’ll start to be able to make sense out of these viruses. Right now, we’re kind of looking at the world through a pinhole camera. It works, but it doesn’t give us a full view. Infectious diseases are a real threat to us and we need to have a much better view,” he says.
Layne and the rapid throughput lab have also been recruited to analyze tens of thousands of samples of the influenza viruses endemic to 10 species of common North American migratory birds, as part of a huge survey being conducted in collaboration with UCLA’s Institute of the Environment, led by Institute Acting Director and Director of the Center for Tropical Research Tom Smith — who was also in Africa doing hands-on science as this story was being written.
Influenza A viruses, those that cause disease in humans, are thought to be perpetuated in wild birds. The birds, which don’t usually show any symptoms of infection, serve as reservoirs for the organisms — particularly for H5N1, or “bird flu,” the highly infectious and deadly influenza A subtype that researchers are most worried could mutate into a strain capable of causing the next influenza epidemic. The birds shed huge quantities of virus into the environment that can then infect other animals, including humans.
“Migratory land birds move across the country; in the fall, they go south, in the spring, they go north. If they are infected with avian influenza, they could be spreading it long distances, and to birds of other species,” says biologist John Pollinger, an associate director of the institute’s Center for Tropical Research and a collaborator on the bird surveillance program. “We’re trying to figure out to what extent these guys have flu, and what types of flu they have,” he says.
We live in a new and dangerous world. The United States has already seen some of the havoc that can be unleashed via bioterror attacks. And it has watched with trepidation as viral flu outbreaks begin to take more and more human lives around the world. That’s why America needs a disease early-warning system. And why a small army of Bruin science action heroes is determined to find and build just such a safeguard.
“The science of disease forecasting is still in its infancy, but we’re not going to wait until it is perfect,” concludes Nathan Wolfe. “We need to start doing something now.”
